TW202120077A - Water-soluble cannabinoids - Google Patents

Abstract

Provided is a composition comprising: (a) a polysorbate, (b) vitamin E TPGS, and (c) a cannabinoid. Also provided is a use of the composition for oral consumption and a method of making the composition.

Description

Water-soluble cannabinoids

The present invention relates to a composition containing cannabinoids, in particular, to a composition containing cannabinoids that can be used for oral ingestion, and a manufacturing method thereof.

Cannabinoids are a group of compounds originally discovered and isolated from cannabis or hemp. The terms "hemp" and "cannabis" refer to the genus Cannabis, which contains three species: Cannabis sativa and Indian hemp. ( Cannabis indica ) and Cannabis ruderalis . All three species belong to the Cannabaceae family ( Cannabaceae ), which also includes Humulus ( Humulus ) or hops. More than 100 different cannabinoids have been isolated, including four Hydrocannabinol (THC), Cannabidiol (CBD) and Cannabidiol (CBN). The discovery of these compounds has led to the discovery of an important neurotransmitter system called the endocannabinoid system. The endocannabinoid system. It is widely distributed in the brain and is believed to be responsible for many important body functions.

THC is the main psychoactive component of cannabis and has well-known effects on pain, appetite enhancement, digestion, mood and processes mediated through the endocannabinoid system. In contrast to THC, CBD does not seem to have psychoactive properties. However, CBD has been shown to have pharmacological effects in models of various pathologies from spontaneous inflammation and neurodegenerative diseases to epilepsy, autoimmune disorders (such as multiple sclerosis), arthritis, schizophrenia, and cancer.

Cannabinoids (such as CBD and THC) have a great preference for non-aqueous media and only dissolve in oils and organic solvents (such as alcohol-based solvents, aliphatic hydrocarbons, dimethyl sulfide, dimethylformamide and acetone) . The lack of solubility in water can lead to low absorption and bioavailability, thereby posing challenges to the administration of therapeutic agents in oral intake. To increase bioavailability and absorption, cannabinoids have been formulated with various excipients. However, the inclusion of such ingredients can produce cannabinoid compositions with low solubility and stability, and can be expensive and difficult to manufacture.

Therefore, there is a need for novel formulations suitable for oral ingestion of cannabinoids (such as CBD and THC) with improved absorption and bioavailability, which are relatively easy to manufacture and maintain storage stability for an extended period of time.

It should be understood that the inventor has established this background description to help readers, and should not be regarded as a reference to the prior art, nor should it be regarded as an indication that the technology itself is aware of any problems pointed out. Although the principles described can in some aspects and embodiments alleviate the problems inherent in other systems, it should be understood that the scope of the protected innovation is defined by the scope of the accompanying patent application, not by the claimed invention to solve the problems in this article. The capacity limit for any particular problem indicated.

The present invention is based at least in part on the use of polysorbate and D-α-tocopherol polyethylene glycol 1000 succinate (vitamin E TPGS)-based formulations to prepare water-soluble cannabinoids. In various embodiments, the present invention provides compositions (e.g., compositions for oral ingestion), such as solid, liquid, or oil formulations, methods for preparing such compositions, and a method for preparing such compositions for oral ingestion use. These compositions include polysorbate, vitamin E TPGS, and cannabinoids (such as CBD or THC). The oral composition may be non-alcoholic or alcoholic (that is, additionally containing ethanol if necessary). The inventors have found that the desired ratio of polysorbate, vitamin E TPGS and cannabinoids is better to produce a reasonably high water-soluble concentration while maintaining a high degree of storage stability.

Therefore, in one aspect, the present invention provides a composition (e.g., solid, liquid or oil) comprising (a) polysorbate, (b) vitamin E TPGS, and (c) cannabinoids, consisting essentially of Its composition, or consists of it.

In another aspect, the present invention also provides a composition (e.g., in liquid form) comprising (a) polysorbate, (b) vitamin E TPGS, (c) cannabinoids (e.g., CBD or THC) , And (d) water, consisting essentially of, or consisting of.

In another aspect, the present invention provides a composition (e.g., solid, liquid or oil) comprising (a) about 30% to about 50% by weight of polysorbate, (b) about 10% by weight To about 30% by weight of Vitamin E TPGS, and (c) about 20% to about 60% by weight of cannabinoids (such as CBD or THC), wherein the weight percentages are based on (a), (b) and (c) The sum total is basically composed of, or composed of.

In another aspect, the present invention also provides a composition (for example, in liquid form), which comprises (a) about 30% to about 50% by weight of polysorbate, (b) about 10% to about 10% by weight About 30% by weight of vitamin E TPGS, (c) about 20% to about 60% by weight of cannabinoids (such as CBD or THC), and (d) water, wherein the weight percentage is based on (a) and (b) The sum of (c) basically consists of or consists of it.

In another aspect, the present invention also provides a use of the composition described herein for oral ingestion.

In another aspect, the present invention further provides a method of manufacturing a composition for oral ingestion, the composition comprising: (a) polysorbate, (b) vitamin E TPGS, and (c) cannabinoids The method includes preparing an aqueous solution containing polysorbate, vitamin E TPGS and cannabinoids, and filtering the aqueous solution to form a filtered aqueous solution.

Embodiments of the present invention provide a cannabinoid-containing composition (for example, solid, liquid, or oil) that can be used for oral ingestion (for example, in a liquid formulation), and a method for preparing the cannabinoid-containing composition. Advantageously, the composition according to the preferred embodiment of the present invention exhibits enhanced stability for an extended period of time. In addition, the composition for oral ingestion according to a preferred embodiment of the present invention can exhibit improved absorption and bioavailability. Therefore, the embodiments of the present invention represent an improvement over the conventional technology. In this regard, as described herein, cannabinoids (such as THC and CBD) may not dissolve in water and therefore require additional components to facilitate dissolution ("solubilizers"). In order to achieve the desired concentration of the cannabinoid in an aqueous solution, and maintain the desired concentration, compositions and methods have been developed as described herein. Other benefits of the method and composition of the present invention should be easily understood from the disclosure provided herein.

An embodiment of the present invention provides a composition comprising: (a) polysorbate, (b) vitamin E TPGS, and (c) cannabinoids.

The composition contains polysorbate. As used herein, the term polysorbate refers to a class of emulsifiers derived from sorbitol. The polysorbate can be any suitable polysorbate of any suitable molecular weight. Therefore, in various embodiments, the polysorbate may have, for example, about 1000 g/mol to about 1400 g/mol (e.g., about 1100 g/mol to about 1400 g/mol, about 1150 g/mol to about 1400 g/mol). mol, about 1200 g/mol to about 1400 g/mol, about 1150 g/mol to about 1350 g/mol, about 1150 g/mol to about 1300 g/mol, about 1200 g/mol to about 1400 g/mol, About 1200 g/mol to about 1350 g/mol, about 1200 g/mol to about 1300 g/mol, or about 1250 g/mol to about 1400 g/mol).

In some embodiments, the polysorbate is polysorbate 20 (polyoxyethylene (20) sorbitan monolaurate), polysorbate 40 (polyoxyethylene (20) sorbitan monolaurate), Palmitate), polysorbate 60 (polyoxyethylene (20) sorbitan monostearate), polysorbate 80 (polyoxyethylene (20) sorbitan monooleate) or Its combination. Although not wishing to be bound by any particular theory, it is believed that in terms of composition stability, polysorbate 20 is superior to polysorbate 40, polysorbate 40 is superior to polysorbate 60, and polysorbate Ester 60 is better than polysorbate 80.

In certain embodiments, the composition includes polysorbate 20. Therefore, the polysorbate may be polysorbate 20 or polysorbate may contain polysorbate 20, and one or more of polysorbate 40, polysorbate 60, and polysorbate 80. By. In other embodiments, the composition includes polysorbate 40. Therefore, the polysorbate may be polysorbate 40 or polysorbate may be polysorbate 40, and one or more of polysorbate 20, polysorbate 60, and polysorbate 80 By.

In a preferred embodiment, the composition comprises polysorbate 20; polysorbate 20 and polysorbate 40; polysorbate 20 and polysorbate 60; or polysorbate 20 and polysorbate Alcohol ester 80.

The composition may contain any suitable amount of polysorbate (ie, the sum of polysorbate). For example, the composition may include about 5 wt% to about 50 wt% polysorbate (that is, the sum of polysorbate), for example, about 10 wt% to about 50 wt%, about 15 wt% to about 50% by weight, about 20% by weight to about 50% by weight, about 25% by weight to about 50% by weight, about 30% by weight to about 50% by weight, about 35% by weight to about 45% by weight, about 5% by weight to about 45 wt%, about 10 wt% to about 45 wt%, about 15 wt% to about 45 wt%, about 20 wt% to about 45 wt%, about 25 wt% to about 50 wt%, about 30 wt% to about 45 wt%, about 35 wt% to about 45 wt%, about 5 wt% to about 40 wt%, about 10 wt% to about 40 wt%, about 15 wt% to about 40 wt%, about 20 wt% to about 40% by weight, about 25% to about 40% by weight, about 30% to about 40% by weight, or about 35% to about 40% by weight of polysorbate (that is, the sum of polysorbate) , Where the weight% is based on the sum of the ingredients except water. In some embodiments, the composition includes about 30% to about 50% by weight of polysorbate (ie, the sum of polysorbate), wherein the weight% is based on the sum of ingredients other than water meter. In certain embodiments, the composition includes about 35% to about 45% by weight of polysorbate, wherein the weight% is based on the sum of ingredients other than water.

The composition contains Vitamin E TPGS. The composition may contain any suitable amount of Vitamin E TPGS. For example, the composition may include about 1% to about 50% by weight of Vitamin E TPGS, for example, about 5% to about 50% by weight, about 10% to about 50% by weight, and about 15% to about 50% by weight. %, about 20% by weight to about 50% by weight, about 25% by weight to about 50% by weight, about 30% by weight to about 50% by weight, about 1% by weight to about 40% by weight, about 5% by weight to about 40% by weight %, about 10% by weight to about 40% by weight, about 15% by weight to about 40% by weight, about 20% by weight to about 40% by weight, about 25% by weight to about 40% by weight, about 30% by weight to about 40% by weight %, about 1% by weight to about 30% by weight, about 5% by weight to about 30% by weight, about 10% by weight to about 30% by weight, about 15% by weight to about 30% by weight, about 20% by weight to about 30% by weight %, about 25% by weight to about 30% by weight, or about 15% by weight to about 25% by weight of vitamin E TPGS, wherein the weight% is based on the sum of ingredients other than water. In some embodiments, the composition includes about 10% to about 30% by weight of Vitamin E TPGS, wherein the weight% is based on the sum of ingredients other than water. In certain embodiments, the composition includes about 15% to about 25% by weight of Vitamin E TPGS, wherein the weight% is based on the sum of ingredients other than water.

The composition contains cannabinoids. Cannabinoids can be isolated from plants of the genus Cannabis (such as dried hemp and/or hemp leaves), which contains three species, namely hemp, hemp, and hemp. The separated extract can be used directly, or the separated extract can be purified (for example, using column chromatography) and/or processed (for example, filtration, dewaxing, decolorization, and/or decarboxylation) before being used in the composition . Therefore, the cannabinoid can be a single purified cannabinoid (such as CBD or THC), a mixture of cannabinoids, or an extract of the cannabis plant. The cannabinoid can be any cannabinoid isolated from the cannabis plant.

The following are common cannabinoids in hemp leaf extract, which can be used in the compositions described herein: THC Tetrahydrocannabinol THCV Tetrahydrocannabinol CBG Cannabidiol CBD Cannabidiol CBC Cannabichromene CBN Cannabidiol THCA Tetrahydrocannabinolic acid CBDA Cannabidiol acid CBGA Cannabidiol CBDV Cannabidiol Therefore, the cannabinoid can be THC, THCV, CBG, CBD, CBC, CBN, THCA, CBDA, CBGA, CBDV, or a combination thereof.

In some embodiments, the cannabinoid is cannabidiol (CBD) and/or tetrahydrocannabinol (THC). In certain embodiments, cannabinoids (such as CBD and/or THC) are purified to a high degree (such as greater than 90% purity, greater than 95% purity, or greater than 99% purity) for use in the composition, thereby allowing them Used in various medical and nutritional applications. In some embodiments, the cannabinoid is THC. In a preferred embodiment, the cannabinoid is CBD. In some aspects, purified CBD can be used, which has the benefits of CBD without the substitution effect of psychoactive THC.

The composition may contain any suitable amount of cannabinoids (ie, the sum of cannabinoids). For example, the composition may include about 1% to about 70% by weight of cannabinoids (that is, the sum of cannabinoids), for example, about 5% to about 70% by weight, about 10% to about 70% by weight, About 15% by weight to about 70% by weight, about 20% by weight to about 70% by weight, about 25% by weight to about 70% by weight, about 30% by weight to about 70% by weight, about 1% by weight to about 60% by weight, About 5% by weight to about 60% by weight, about 10% by weight to about 60% by weight, about 15% by weight to about 60% by weight, about 20% by weight to about 60% by weight, about 25% by weight to about 60% by weight, About 30% by weight to about 60% by weight, about 1% by weight to about 50% by weight, about 5% by weight to about 50% by weight, about 10% by weight to about 50% by weight, about 15% by weight to about 50% by weight, About 20% by weight to about 50% by weight, about 25% by weight to about 50% by weight, or about 30% by weight to about 50% by weight of cannabinoids (that is, the sum of cannabinoids), wherein the weight% is based on The sum of the components other than water. In some embodiments, the composition includes about 20% to about 60% by weight of cannabinoids (ie, the sum of cannabinoids), wherein the weight% is based on the sum of ingredients other than water. In certain embodiments, the composition includes about 30% to about 50% by weight of cannabinoids (ie, the sum of cannabinoids), wherein the weight% is based on the sum of ingredients other than water.

In some embodiments, the composition includes about 30% to about 50% by weight of polysorbate (that is, the sum of polysorbate), about 10% to about 30% by weight of vitamin E TPGS, And about 20% to about 60% by weight of cannabinoids (that is, the sum of cannabinoids), wherein the weight percentage is based on polysorbates (that is, the sum of polysorbates), vitamin E TPGS and hemp The sum of the elements (that is, the sum of cannabinoids). In certain embodiments, the composition comprises about 35% to about 45% by weight of polysorbate (that is, the sum of polysorbate), about 15% to about 25% by weight of vitamin E TPGS , And about 30% to about 50% by weight of cannabinoids (that is, the sum of cannabinoids), wherein the weight percentage is based on polysorbate (that is, the sum of polysorbate), vitamin E TPGS and The sum total of cannabinoids (that is, the sum of cannabinoids).

The composition can be solid, oil or aqueous solution. Therefore, the composition described herein may further comprise water. The water can be any type of water suitable for oral ingestion. For example, the water can be purified (for example, by filtration, distillation, or reverse osmosis), carbonated, dyed, flavored, or any combination thereof. When the composition is an aqueous solution, the aqueous solution may have about 0.05 mg/mL to about 20 mg/mL, about 0.05 mg/mL to about 10 mg/mL, about 0.05 mg/mL to about 5 mg/mL, or about Concentrations of cannabinoids (such as CBD and/or THC) ranging from 0.05 mg/mL to about 1 mg/mL.

The concentration of cannabinoids in the composition can be measured by any suitable method. In some embodiments, the concentration of cannabinoids in the composition is analyzed by high performance liquid chromatography ("HPLC"). The skilled artisan should know the parameters suitable for analyzing the composition by HPLC so that the amount of cannabinoids in the composition can be determined.

In some embodiments, the compositions described herein are stable on storage for an extended period of time. For example, the composition described herein can be stored and stabilized for at least 1 month, at least 3 months, at least 6 months, at least 1 year, at least 2 years, or at least 5 years. As used herein, the phrase "storage stability" means that a composition enclosed in an aluminum, plastic or glass container maintains at least about 90% of the cannabinoid concentration of the original composition during the storage period (for example, the cannabinoid of the original composition). The concentration is at least about 95%). In certain embodiments, the composition is stable when stored at 4°C for at least 3 months (e.g., at least 6 months, at least 1 year, at least 2 years, or at least 5 years). In other embodiments, the composition is stable when stored at 23°C for at least 3 months (e.g., at least 6 months, at least 1 year, at least 2 years, or at least 5 years). In some embodiments, the composition is stable when stored at 37°C for at least 3 months (e.g., at least 6 months, at least 1 year, at least 2 years, or at least 5 years). The stability of the composition can also be qualitatively monitored by color. Without wishing to be bound by any particular theory, it is believed that cannabinoids can oxidize over time, which in turn causes the solution to turn yellow. The compositions described herein are intended to reduce the aforementioned oxidation process, thereby reducing color changes.

The composition may further comprise one or more pharmaceutically acceptable excipients. Suitable excipients and dosages can be easily determined based on experience and consideration of standard procedures and reference works in related fields (such as sweeteners, dyes, correctives, and preservatives) under the guidance of ordinary technicians.

The compositions described herein can be used for oral ingestion. For example, the compositions can be used in foods (such as cooking ingredients, baked goods, energy bars, etc.) and beverages (such as energy drinks, hydrated beverages, alcoholic beverages, etc.). In some embodiments, especially when the cannabinoid does not contain THC (for example, it contains CBD), the composition is an alcoholic beverage for oral ingestion. Therefore, in some embodiments, the composition described herein may further comprise ethanol.

For compositions containing ethanol, the composition may contain ethanol in an amount of about 5 mL to about 50 mL/100 mL of water. For example, the composition may include ethanol in an amount of about 5 mL to about 40 mL/100 mL water, about 5 mL to about 30 mL/100 mL water, about 5 mL to about 20 mL/100 mL water, about 10 mL mL to about 50 mL/100 mL water, about 10 mL to about 40 mL/100 mL water, about 10 mL to about 30 mL/100 mL water, or about 10 mL to about 20 mL/100 mL water.

When the composition basically consists of certain components, in addition to trace amounts of water and/or ethanol, other components that exert material effects (such as changing the solubility or stability of cannabinoids) are excluded from the composition. When a composition for oral ingestion consists of certain ingredients, if not explicitly included, the composition does not contain any other components, including water and/or ethanol.

The present invention further provides a method of manufacturing a composition for oral ingestion, the composition comprising: (a) polysorbate, (b) vitamin E TPGS, and (c) cannabinoids, the method comprising: preparing a composition comprising An aqueous solution of polysorbate, vitamin E TPGS and cannabinoids, and filtering the aqueous solution to form a filtered aqueous solution. The final concentrations of (a) polysorbate, (b) vitamin E TPGS, and (c) cannabinoids in the composition are consistent with the values described herein.

The aqueous solution can be filtered by any suitable technique to remove residual particles in the aqueous solution. In some embodiments, the aqueous solution is filtered using a microfilter. For example, the aqueous solution can have at least about 0.1 µm (e.g., at least about 0.2 µm, at least about 0.3 µm, at least about 0.4 µm, at least about 0.5 µm, at least about 0.6 µm, at least about 0.7 µm, at least about 0.8 µm, at least about The particles of 0.9 µm or at least about 1 µm) are retained by a filter (such as a microfiber filter). In some embodiments, the aqueous solution is ^{filtered using a Whatman™} glass microfiber filter and/or a polyether sulfide (PES) filter. In some embodiments, the aqueous solution is ^{filtered using a 0.7 µm Whatman™} glass microfiber filter, a 0.2 µm polyether sludge (PES) filter, a 0.22 µm polyether sludge (PES) filter, or a combination thereof.

In some embodiments, the method further includes diluting the filtered aqueous solution to form a diluted aqueous solution. The filtered aqueous solution can be diluted with water and/or alcohol. Without wishing to be bound by any particular theory, it is believed that the undiluted composition (ie, the stock solution) may be too concentrated for oral ingestion, and may need to be diluted.

In some embodiments, the method further includes removing at least a portion of water from the filtered aqueous solution to form a concentrated aqueous solution. The water can be removed by any suitable method. For example, water can be removed by evaporation (e.g., under reduced pressure, high temperature, or a combination thereof), membrane permeation (e.g., nanofiltration), or a combination thereof. The concentrated aqueous solution may contain water, may be substantially free of water, or may be free of water. Therefore, the concentrated aqueous solution can be an aqueous solution, oil, or solid. The concentrated aqueous solution can be used as a concentrate for storage and transportation purposes. For example, the concentrated aqueous solution can be a powder, which can be packaged and then dissolved in water and/or alcohol (e.g., by the user) to form a composition for oral ingestion.

In some embodiments, the method further comprises adding a pharmaceutically acceptable excipient to the aqueous solution, filtered aqueous solution, diluted aqueous solution, concentrated aqueous solution, or a combination thereof.

In some embodiments, the method further includes adding ethanol to the aqueous solution, filtered aqueous solution, diluted aqueous solution, concentrated aqueous solution, or a combination thereof.

In some embodiments, the method includes packaging a composition described herein. The composition can be packaged in any suitable container (e.g., aluminum, plastic, glass, cardboard, paper, etc.). The packaged composition can be stored and/or transported at any suitable temperature. In some embodiments, the packaged composition is stored and/or transported at a temperature of about 37°C or lower, for example, about 30°C or lower, or about 23°C or lower. In a preferred embodiment, the packaged composition is stored at a temperature of about 30°C or lower.

On the whole, the self-disclosure as a whole should easily clarify the amount of polysorbate, vitamin E TPGS, and cannabinoids (such as CBD and/or THC) suitable for the method described herein. Example

The principles of the present disclosure are incorporated into the following non-limiting examples of embodiments:

Example (1) A composition comprising: (a) polysorbate, (b) vitamin E TPGS, and (c) cannabinoids.

Example (2) The composition as in Example (1), which contains: (a) about 30% to about 50% by weight of polysorbate, (b) about 10% to about 30% by weight of vitamins E TPGS, and (c) about 20% to about 60% by weight of cannabinoids, wherein the weight percentage is based on the sum of (a), (b) and (c).

Example (3) The composition as in Example (2), which contains: (a) about 35% to about 45% by weight of polysorbate, (b) about 15% to about 25% by weight of vitamins E TPGS, and (c) about 30% to about 50% by weight of cannabinoids, wherein the weight percentage is based on the sum of (a), (b) and (c).

Embodiment (4) The composition according to any one of embodiments (1) to (3), wherein the polysorbate is polysorbate 20, polysorbate 40, polysorbate 60, polysorbate Alcohol ester 80 or a combination thereof.

Embodiment (5) The composition according to any one of embodiments (1) to (4), wherein the polysorbate is polysorbate 20, polysorbate 40, polysorbate 60, and polysorbate One or more of sorbitol ester 80.

Embodiment (6) The composition according to any one of embodiments (1) to (4), wherein the polysorbate is polysorbate 20.

Embodiment (7) The composition according to any one of embodiments (1) to (4), wherein the polysorbate is polysorbate 40, polysorbate 20, polysorbate 60, and polysorbate One or more of sorbitol ester 80.

Embodiment (8) The composition according to any one of embodiments (1) to (4), wherein the polysorbate is polysorbate 40.

Embodiment (9) The composition according to any one of embodiments (1) to (8), wherein the cannabinoid is cannabidiol, tetrahydrocannabinol or a combination thereof.

Embodiment (10) is the composition of any one of embodiments (1) to (9), wherein the cannabinoid is cannabidiol.

Embodiment (11) is the composition of any one of embodiments (1) to (9), wherein the cannabinoid is tetrahydrocannabinol.

Embodiment (12) Like the composition of any one of embodiments (1) to (11), wherein the composition is solid.

Embodiment (13) is the composition of any one of embodiments (1) to (11), wherein the composition is oil.

Embodiment (14) is the composition of any one of embodiments (1) to (11), wherein the composition is an aqueous solution.

Embodiment (15) is the composition of embodiment (14), wherein the aqueous solution has a cannabinoid concentration of about 0.05 mg/mL to about 20 mg/mL.

Embodiment (16) is the composition of embodiment (15), wherein the aqueous solution has a cannabinoid concentration of about 0.05 mg/mL to about 10 mg/mL.

Embodiment (17) is the composition of embodiment (16), wherein the aqueous solution has a cannabinoid concentration of about 0.05 mg/mL to about 5 mg/mL.

Embodiment (18) is the composition of embodiment (17), wherein the aqueous solution has a cannabinoid concentration of about 0.05 mg/mL to about 1 mg/mL.

Embodiment (19) is the composition of any one of embodiments (1) to (18), wherein the composition further comprises one or more pharmaceutically acceptable excipients.

Example (20) A use of the composition as in any one of Examples (1) to (19) for oral ingestion.

Example (21) A method of manufacturing a composition for oral ingestion, the composition comprising: (a) polysorbate, (b) vitamin E TPGS, and (c) cannabinoids, the method comprising: preparing An aqueous solution containing polysorbate, vitamin E TPGS and cannabinoids, and filtering the aqueous solution to form a filtered aqueous solution.

Embodiment (22) is the method of embodiment to (21), wherein the polysorbate is polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, or a combination thereof.

Embodiment (23) is the method of embodiment (21) or embodiment (22), wherein the polysorbate is polysorbate 20, and polysorbate 40, polysorbate 60, and polysorbate One or more of 80.

Embodiment (24) is the method of embodiment (21) or embodiment (22), wherein the polysorbate is polysorbate 20.

Embodiment (25) is the method of embodiment (21) or embodiment (22), wherein the polysorbate is polysorbate 40, polysorbate 20, polysorbate 60, and polysorbate One or more of 80.

Embodiment (26) is the method of embodiment (21) or embodiment (22), wherein the polysorbate is polysorbate 40.

Embodiment (27) is the method of any one of embodiments (21) to (26), wherein the cannabinoid is cannabidiol, tetrahydrocannabinol, or a combination thereof.

Embodiment (28) Like the method of embodiment (27), wherein the cannabinoid is cannabidiol.

Embodiment (29) Like the method of embodiment (27), wherein the cannabinoid is tetrahydrocannabinol.

Embodiment (30) Like the method in any one of Embodiments (21) to (29), the method further includes diluting the filtered aqueous solution to form a diluted aqueous solution.

Embodiment (31) Like the method of any one of embodiments (21) to (29), the method further includes removing at least a portion of water from the filtered aqueous solution to form a concentrated aqueous solution.

Embodiment (32) Like the method of embodiment (31), wherein the concentrated aqueous solution is a solid.

Embodiment (33) Like the method of embodiment (31), wherein the concentrated aqueous solution is oil.

Embodiment (34) Like the method in any one of Embodiments (21) to (33), the method further comprises adding a pharmaceutically acceptable excipient to the aqueous solution, the filtered aqueous solution, the diluted aqueous solution, Concentrated aqueous solution or a combination thereof.

The foregoing exemplary embodiments numbered 1 to 34 of the present disclosure are non-limiting. Other exemplary embodiments are apparent from the overall description herein. As those skilled in the art will understand after reading the present disclosure, each individually numbered embodiment can be used or combined with any of the previous or subsequent individually numbered aspects.

The following examples further illustrate the present invention, but of course should not be construed as limiting its scope in any way. Example 1

This example illustrates a method for preparing a water-soluble cannabidiol composition containing polysorbate 20, vitamin E TPGS, and cannabidiol.

Polysorbate 20 (15 mL) was added to high performance liquid chromatography (HPLC) water (985 mL) at 50°C. Vitamin E TPGS (7.5 g) was added to the resulting mixture and the mixture was stirred at 50°C for 30 to 60 minutes. Cannabidiol (15 g) was slowly added at 50°C and the resulting composition was mixed for 16 hours. The resulting mixture was filtered through a 0.7 µm Whatman ^TM glass microfiber filter, followed by a 0.2 µm polyether sulfide (PES) filter to produce a composition containing 8.7 mg/mL cannabidiol. The composition was diluted 83.33 times in water and filtered through a 0.22 µm polyether sulfide (PES) filter to produce a composition containing 0.104 mg/mL cannabidiol.

Use HPLC to analyze the diluted solution containing polysorbate 20, vitamin E TPGS and cannabidiol using the following parameters: Sample: Inject 20 µl Column: Reliasil, C18, 3 µm, 4.6 x 150 mm Temperature: 25℃ Wavelength: 220 nm Mobile phase: A: 0.2% phosphoric acid in water, B: ACN gradient starting from 80:20 (B:A) for 20 min. The resulting HPLC trace is shown in Figure 1. Example 2

This example illustrates the stability of a concentrated composition containing polysorbate 20, vitamin E TPGS and cannabidiol.

The stock composition of Example 1 containing polysorbate 20, vitamin E TPGS and 8.7 mg/mL cannabidiol was stored at three different temperatures of 4°C, room temperature (that is, about 23°C), and 37°C. On day 0 and day 84, the stock solutions at each of these temperatures were diluted 83.33 times in drinking water and analyzed using the HPLC parameters shown in Example 1. The results are shown in Figure 2.

The results shown in Figure 2 should be clear, the concentrated composition containing polysorbate 20, vitamin E TPGS and 8.7 mg/mL cannabidiol is stable, resulting in 4 ℃, room temperature (ie About 23°C) and 37°C, the loss of cannabidiol is minimal. Example 3

This example illustrates the stability of a diluted composition containing polysorbate 20, vitamin E TPGS and cannabidiol.

Store the diluted composition of Example 1 containing polysorbate 20, vitamin E TPGS and 0.104 mg/mL cannabidiol at three different temperatures of 4°C, room temperature (ie about 23°C) and 37°C . The HPLC parameters shown in Example 1 were used to analyze the diluted composition at each of these temperatures on Day 0 and Day 35. The results are shown in Figure 3.

The results shown in Figure 3 should be clear, at 4°C and room temperature (that is, about 23°C), compared to the concentrated composition of Example 2, it contains polysorbate 20, vitamin E TPGS The diluted composition with 0.104 mg/mL cannabidiol maintains considerable stability, resulting in minimal loss of cannabidiol. Example 4

This example illustrates a method for preparing a water-soluble cannabidiol composition containing polysorbate 20, polysorbate 40, vitamin E TPGS, and cannabidiol.

Polysorbate 20 (7.5 mL) and polysorbate 40 (7.5 mL) were added to high performance liquid chromatography (HPLC) water (985 mL) at 50°C. Vitamin E TPGS (7.5 g) was added to the resulting mixture and the mixture was stirred at 50°C for 30 to 60 minutes. Cannabidiol (15 g) was slowly added at 50°C and the resulting composition was mixed for 16 hours. The resulting mixture was filtered through a 0.7 µm Whatman ^TM glass microfiber filter, followed by a 0.2 µm polyether sulfide (PES) filter to produce a composition containing 8.44 mg/mL cannabidiol. The composition was diluted 83.33 times in water and filtered through a 0.22 µm polyether sulfide (PES) filter to produce a composition containing 0.101 mg/mL cannabidiol. The diluted composition containing 0.101 mg/mL cannabidiol was analyzed using the HPLC parameters shown in Example 1. Example 5

This example illustrates the stability of a concentrated composition containing polysorbate 20, polysorbate 40, vitamin E TPGS and cannabidiol.

Example 4 containing polysorbate 20, polysorbate 40, vitamin E TPGS and 8.44 mg/mL cannabidiol stored at three different temperatures of 4°C, room temperature (ie about 23°C) and 37°C The reserve composition. On day 0 and day 8, the stock solutions at each of these temperatures were diluted 83.33 times in drinking water and analyzed using the HPLC parameters shown in Example 1. The results are shown in Figure 4.

As can be seen from the results shown in Figure 4, the concentrated composition containing polysorbate 20, polysorbate 40, vitamin E TPGS and 8.44 mg/mL cannabidiol is stable, resulting in a temperature of 4°C , Room temperature (that is, about 23°C) and 37°C, the loss of cannabidiol is minimal. Example 6

This example illustrates the stability of a diluted composition containing polysorbate 20, polysorbate 40, vitamin E TPGS and cannabidiol.

Example 4 containing polysorbate 20, polysorbate 40, vitamin E TPGS and 0.101 mg/mL cannabidiol stored at three different temperatures of 4°C, room temperature (ie about 23°C) and 37°C The diluted composition. The HPLC parameters shown in Example 1 were used to analyze the diluted composition at each of these temperatures on Day 0 and Day 8. The results are shown in Figure 5.

The results shown in Figure 5 should be clear. At 4°C, compared to the concentrated composition of Example 5, it contains polysorbate 20, polysorbate 40, vitamin E TPGS and 0.101 mg/mL cannabis. The diluted composition of diphenols maintains considerable stability, resulting in minimal loss of cannabidiol. Example 7

This example illustrates a method for preparing a water-soluble cannabidiol composition containing polysorbate 20, polysorbate 60, vitamin E TPGS, and cannabidiol.

Polysorbate 20 (7.5 mL) and polysorbate 60 (7.5 mL) were added to high performance liquid chromatography (HPLC) water (985 mL) at 50°C. Vitamin E TPGS (7.5 g) was added to the resulting mixture and the mixture was stirred at 50°C for 30 to 60 minutes. Cannabidiol (15 g) was slowly added at 50°C and the resulting composition was mixed for 16 hours. The resulting mixture was filtered through a 0.7 µm Whatman ^TM glass microfiber filter, followed by a 0.2 µm polyether sulfide (PES) filter to produce a composition containing 10.05 mg/mL cannabidiol. The composition was diluted 83.33 times in water and filtered through a 0.22 µm polyether sulfide (PES) filter to produce a composition containing 0.12 mg/mL cannabidiol. The diluted composition containing 0.12 mg/mL cannabidiol was analyzed using the HPLC parameters shown in Example 1. Example 8

This example illustrates the stability of a concentrated composition containing polysorbate 20, polysorbate 60, vitamin E TPGS and cannabidiol.

Example 7 containing polysorbate 20, polysorbate 60, vitamin E TPGS and 10.05 mg/mL cannabidiol stored at three different temperatures of 4°C, room temperature (that is, about 23°C) and 37°C The reserve composition. On day 0 and day 15, the stock solutions at each of these temperatures were diluted 83.33 times in drinking water and analyzed using the HPLC parameters shown in Example 1. The results are shown in Figure 6.

As is clear from the results shown in Figure 6, the concentrated composition containing polysorbate 20, polysorbate 60, vitamin E TPGS and 10.05 mg/mL cannabidiol is stable, resulting in a stable temperature at 4°C. , Room temperature (that is, about 23°C) and 37°C, the loss of cannabidiol is minimal. Example 9

This example illustrates the stability of a diluted composition containing polysorbate 20, polysorbate 60, vitamin E TPGS and cannabidiol.

Example 7 containing polysorbate 20, polysorbate 60, vitamin E TPGS and 0.12 mg/mL cannabidiol stored at three different temperatures of 4°C, room temperature (that is, about 23°C) and 37°C The diluted composition. The HPLC parameters shown in Example 1 were used to analyze the diluted composition at each of these temperatures on Day 0 and Day 15. The results are shown in Figure 7.

As is clear from the results shown in Figure 7, at 4°C, relative to the concentrated composition of Example 8, it contains polysorbate 20, polysorbate 60, vitamin E TPGS and 0.12 mg/mL cannabis The diluted composition of diphenols maintains considerable stability, resulting in minimal loss of cannabidiol. Example 10

This example illustrates a method for preparing a water-soluble cannabidiol composition containing polysorbate 20, polysorbate 80, vitamin E TPGS, and cannabidiol.

Polysorbate 20 (7.5 mL) and polysorbate 80 (7.5 mL) were added to high performance liquid chromatography (HPLC) water (985 mL) at 50°C. Vitamin E TPGS (7.5 g) was added to the resulting mixture and the mixture was stirred at 50°C for 30 to 60 minutes. Cannabidiol (15 g) was slowly added at 50°C and the resulting composition was mixed for 16 hours. The resulting mixture was filtered through a 0.7 µm Whatman ^TM glass microfiber filter, followed by a 0.2 µm polyether sulfide (PES) filter to produce a composition containing 8.41 mg/mL cannabidiol. The composition was diluted 83.33 times in water and filtered through a 0.22 µm polyether sulfide (PES) filter to produce a composition containing 0.101 mg/mL cannabidiol. The diluted composition containing 0.101 mg/mL cannabidiol was analyzed using the HPLC parameters shown in Example 1. The resulting HPLC trace is shown in Figure 8. Example 11

This example illustrates the stability of a concentrated composition containing polysorbate 20, polysorbate 80, vitamin E TPGS and cannabidiol.

Example 10 containing polysorbate 20, polysorbate 80, vitamin E TPGS and 8.41 mg/mL cannabidiol stored at three different temperatures of 4°C, room temperature (ie about 23°C) and 37°C The reserve composition. On day 0 and day 19, the stock solutions at each of these temperatures were diluted 83.33 times in drinking water and analyzed using the HPLC parameters shown in Example 1. The results are shown in Figure 9.

As shown in the results shown in Figure 9, it should be clear that the concentrated composition containing polysorbate 20, polysorbate 80, vitamin E TPGS and 8.41 mg/mL cannabidiol is stable, resulting in 4°C , Room temperature (that is, about 23°C) and 37°C, the loss of cannabidiol is minimal. Example 12

This example illustrates the stability of a diluted composition containing polysorbate 20, polysorbate 80, vitamin E TPGS and cannabidiol.

Example 10 containing polysorbate 20, polysorbate 80, vitamin E TPGS and 0.101 mg/mL cannabidiol stored at three different temperatures of 4°C, room temperature (ie about 23°C) and 37°C The diluted composition. The HPLC parameters shown in Example 1 were used to analyze the diluted composition at each of these temperatures on Day 0 and Day 19. The results are shown in Figure 10.

The results shown in Figure 10 should be clear, at 4°C, compared to the concentrated composition of Example 11, containing polysorbate 20, polysorbate 80, vitamin E TPGS and 0.12 mg/mL cannabis The diluted composition of diphenols maintains considerable stability, resulting in minimal loss of cannabidiol.

All references cited herein (including publications, patent applications, and patents) are incorporated herein by reference to the extent that each reference is individually and specifically indicated as being incorporated by reference and with The full text is shown in this article.

Unless otherwise indicated herein or clearly contradictory to the context, the terms "a" and "an" and "the" and "at least one" and "at least one" are used in the context of describing the present invention (especially in the context of the scope of subsequent patent applications). Similar indicators should be interpreted as covering both singular and plural numbers. Unless otherwise indicated herein or clearly contradictory to the context, use of the term "at least one" followed by a list of one or more items (for example, "at least one of A and B") should be interpreted as meaning selected from the listed items One item (A or B) or any combination of two or more of the listed items (A and B). Unless otherwise specified, the terms "including", "having", "including" and "containing" shall be interpreted as opening terms (that is, meaning "including but not limited to"). Unless otherwise indicated herein, the description of the numerical range herein is only intended to serve as a shorthand method for individually referring to each individual value falling within the range, and each individual value is incorporated into this specification as if it were used herein Stated separately. Unless otherwise indicated herein or clearly contradictory to the context, all methods described herein can be performed in any suitable order. Unless otherwise claimed, the use of any and all examples or exemplary language (such as "such as") provided herein is only intended to better illustrate the present invention and does not limit the scope of the present invention. Any language in this specification should not be construed as indicating any unclaimed elements that are indispensable for practicing the present invention.

This document describes preferred embodiments of the present invention, including the best mode known to the inventor for implementing the present invention. Those skilled in the art can understand the changes of their preferred embodiments after reading the foregoing description. The inventor expects a skilled artisan to appropriately adopt such changes, and the inventor wishes to practice the present invention in other ways than those specifically described herein. Therefore, the present invention includes all modifications and equivalents of the subject matter described in the scope of the attached patent application permitted by applicable laws. In addition, unless otherwise indicated herein or clearly contradicted by the context, the present invention encompasses any combination of the above-mentioned elements in all possible variations thereof.

Figure 1 is a high performance liquid chromatography trace of a diluted sample of a diluted composition containing polysorbate 20, vitamin E TPGS and cannabidiol as described in Example 1.

Figure 2 shows the stability analysis of a concentrated composition containing polysorbate 20, vitamin E TPGS and cannabidiol as described in Example 2 after 84 days of CBD concentration (Y axis) versus temperature (X axis) ).

Figure 3 is the stability analysis of the stability analysis of the diluted composition containing polysorbate 20, vitamin E TPGS and cannabidiol as described in Example 3 after 35 days. CBD concentration (Y axis) vs. temperature (X axis) ) Of the figure.

Figure 4 shows the CBD concentration (Y axis) of the stability analysis of the concentrated composition containing polysorbate 20, polysorbate 40, vitamin E TPGS and cannabidiol as described in Example 5 after 8 days ) Plot of temperature (X axis).

Figure 5 shows the CBD concentration (Y axis) of the stability analysis of the diluted composition containing polysorbate 20, polysorbate 40, vitamin E TPGS and cannabidiol as described in Example 6 after 8 days ) Plot of temperature (X axis).

Figure 6 shows the CBD concentration (Y axis) of the stability analysis of the concentrated composition containing polysorbate 20, polysorbate 60, vitamin E TPGS and cannabidiol as described in Example 8 after 15 days ) Plot of temperature (X axis).

Figure 7 is the CBD concentration (Y axis) of the stability analysis of the diluted composition containing polysorbate 20, polysorbate 60, vitamin E TPGS and cannabidiol as described in Example 9 after 15 days ) Plot of temperature (X axis).

Figure 8 is a high performance liquid chromatography trace of a diluted sample containing a diluted composition of Polysorbate 20, Polysorbate 80, Vitamin E TPGS and Cannabidiol as described in Example 10.

Figure 9 is the stability analysis of the CBD concentration (Y axis) of the concentrated composition containing polysorbate 20, polysorbate 80, vitamin E TPGS and cannabidiol as described in Example 11 after 19 days ) Plot of temperature (X axis).

Figure 10 shows the CBD concentration of the stability analysis of the diluted composition containing polysorbate 20, polysorbate 80, vitamin E TPGS and cannabidiol as described in Example 12 after 19 days (Y axis ) Plot of temperature (X axis).

Claims (33)

A composition comprising: (a) Polysorbate, (b) Vitamin E TPGS, and (c) Cannabinoids. Such as the composition of claim 1, which comprises: (a) about 30% to about 50% by weight of polysorbate, (b) Vitamin E TPGS of about 10% to about 30% by weight, and (c) about 20% to about 60% by weight of cannabinoids, The weight percentage is based on the sum of (a), (b) and (c). Such as the composition of claim 2, which comprises: (a) about 35% to about 45% by weight of polysorbate, (b) Vitamin E TPGS of about 15% to about 25% by weight, and (c) about 30% to about 50% by weight cannabinoids, The weight percentage is based on the sum of (a), (b) and (c). The composition of claim 1, wherein the polysorbate is polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, or a combination thereof. The composition of claim 1, wherein the polysorbate is polysorbate 20, and one or more of polysorbate 40, polysorbate 60, and polysorbate 80. The composition of claim 1, wherein the polysorbate is polysorbate 20. The composition of claim 1, wherein the polysorbate is polysorbate 40, and one or more of polysorbate 20, polysorbate 60, and polysorbate 80. The composition of claim 1, wherein the polysorbate is polysorbate 40. The composition of claim 1, wherein the cannabinoid is cannabidiol, tetrahydrocannabinol or a combination thereof. The composition of claim 1, wherein the cannabinoid is cannabidiol. The composition of claim 1, wherein the cannabinoid is tetrahydrocannabinol. The composition of claim 1, wherein the composition is solid. The composition of claim 1, wherein the composition is oil. The composition of claim 1, wherein the composition is an aqueous solution. The composition of claim 14, wherein the aqueous solution has a cannabinoid concentration of about 0.05 mg/mL to about 20 mg/mL. The composition of claim 15, wherein the aqueous solution has a cannabinoid concentration of about 0.05 mg/mL to about 10 mg/mL. The composition of claim 16, wherein the aqueous solution has a cannabinoid concentration of about 0.05 mg/mL to about 5 mg/mL. The composition of claim 17, wherein the aqueous solution has a cannabinoid concentration of about 0.05 mg/mL to about 1 mg/mL. The composition of claim 1, wherein the composition further comprises one or more pharmaceutically acceptable excipients. A method of manufacturing a composition for oral ingestion, the composition comprising: (a) Polysorbate, (b) Vitamin E TPGS, and (c) Cannabinoids, The method includes: Preparing an aqueous solution containing polysorbate, vitamin E TPGS and cannabinoids, and The aqueous solution is filtered to form a filtered aqueous solution. The method of claim 20, wherein the polysorbate is polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, or a combination thereof. The method of claim 20, wherein the polysorbate is polysorbate 20, and one or more of polysorbate 40, polysorbate 60, and polysorbate 80. The method of claim 20, wherein the polysorbate is polysorbate 20. The method of claim 20, wherein the polysorbate is polysorbate 40, and one or more of polysorbate 20, polysorbate 60, and polysorbate 80. The method of claim 20, wherein the polysorbate is polysorbate 40. The method of claim 20, wherein the cannabinoid is cannabidiol, tetrahydrocannabinol, or a combination thereof. Such as the method of claim 26, wherein the cannabinoid is cannabidiol. Such as the method of claim 26, wherein the cannabinoid is tetrahydrocannabinol. The method of claim 20, the method further comprising diluting the filtered aqueous solution to form a diluted aqueous solution. The method of claim 20, the method further comprising removing at least a portion of the water from the filtered aqueous solution to form a concentrated aqueous solution. The method of claim 30, wherein the concentrated aqueous solution is a solid. The method of claim 30, wherein the concentrated aqueous solution is oil. The method of claim 20, the method further comprising adding a pharmaceutically acceptable excipient to the aqueous solution, the filtered aqueous solution, the diluted aqueous solution, the concentrated aqueous solution, or a combination thereof.

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